MMB vol.151 Clark I.M. (eds.) Matrix Metallo....pdf

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1、MethodsinMolecularBiologyMethodsinMolecularBiologyTMVOLUME151MatrixMatrixMetalloproteinaseMetalloproteinaseProtocolsProtocolsEditedbyEditedbyIanM.ClarkIanM.ClarkHUMANAPRESSHUMANAPRESSMMPsandTIMPs–AnHistoricalPerspective11MMPsandTIMPsAnHistoricalPerspectiveJ.FrederickWoessner,Jr.1.Introdu

2、ctionThematrixmetalloproteinasefieldhasaclearlydefinedstartingpoint,theseminalstudyofJeromeGrossandCharlesLapièrein1962(1)inwhichfrag-mentsofresorbingtadpoletailwereculturedonreconstitutedcollagengels.Acollagenolyticenzymewasrecoveredfromtheculturemediumwhichcouldattacknativecollagenfibr

3、ils.Withinashorttimethesestudieswereextendedtoshowasimilaractivityinawidevarietyoftissues,thatthecollagenmol-eculewascutinto3/4-and1/4-lengthfragments,andthattheenzymeactivitywasdependentonmetalions.Thetissueinhibitorsofmetalloproteinaseswerediscoveredinthefollowingdecadeintissueculture(

4、2)andserum(3).Itwassoonrecognizedthatthematrixmetalloproteinases(MMPs)areinvolvedinagreatmanyprocessesofnormaldevelopmentandgrowthandinpathologicalprocessessuchasarthritisandcancermetastasisastabulatedinWoessner,1998(4).Thishasresultedinatremendousoutpouringofstudiesnownumberingabout10,0

5、00referenceswith1,000appearingeachyear.TherehavebeenmanyrecentreviewsoftheMMPs,includinganentirebook—MatrixMetallopro-teinases—editedbyParksandMecham(5)(1998)anddetailedchaptersinTheHandbookofProteolyticEnzymes(6)andMethodsofEnzymologyVol.248(7).Thesewillbecitedatappropriatepointsbelow.T

6、herearenowatleast18distinctvertebrateMMPs.Thisgroupwasoriginallydefinedonthebasisofdependenceonzincforcatalyticactivityandthepresenceofalargepropeptideresponsibleforlatency.Therecognitionofotherenzymeswithsuchproperties(e.g.,reprolysins)hasledtothedefini-tionofthegrouponthebasisofDNAsequ

7、ence.AsoutlinedintheHandbookFrom:MethodsinMolecularBiology,vol.151:MatrixMetalloproteinaseProtocolsEditedby:I.Clark©HumanaPressInc.,Totowa,NJ12WoessnerofProteolyticEnzymes(6)pp.1144–1147,thematrixinsubfamilyandtheserralysinsubfamilyaregroupedtogetherinfamilyM10ofthemetal-